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Smoldering Plasma Cell MyelomaPhase 2NCT03952832

Leflunomide in Treating Patients With High-Risk Smoldering Multiple Myeloma

A Phase 2 study testing Leflunomide, Quality-of-Life Assessment and Questionnaire Administration in people with Smoldering Plasma Cell Myeloma, run by City of Hope Medical Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase II trial studies how well leflunomide works in treating patients with high-risk smoldering multiple myeloma. Leflunomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Smoldering Plasma Cell Myeloma
What is being tested?
Leflunomide, Quality-of-Life Assessment and Questionnaire Administration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
11 Dec 2019to 11 Jun 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All subjects must have the ability to understand and the willingness to sign a written informed consent
  • Patients must have a life expectancy of > 3 months
  • Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Patients must have a diagnosis of high risk smoldering multiple myeloma, as defined below:
  • The presence of >= 2 of the following risk factors:
  • Bone marrow plasma cell percentage (BMPC%) > 20%
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  • Serum M-protein > 2 g/dL
  • Free light chain ratio (FLCr) > 20
  • At least 2 weeks from prior therapy to time of start of treatment; prior therapy includes steroids (except prednisone or equivalent - up to 10 mg per day is allowed)
  • Platelet count >= 50,000/uL. Platelet transfusions are not allowed within 14 days of platelet assessment
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.0 x upper limits of normal (ULN)
  • Total bilirubin < 1.5 x ULN
  • Calculated creatinine clearance (CrCl) >= 30 mL/min per 24-hour urine collection or the Cockcroft-Gault formula
  • Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential* only), to be performed locally within the screening period
  • A female of childbearing potential is defined as a sexually mature woman who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months
  • Negative for tuberculosis antigen (e.g. T-Spot test)
  • Negative for hepatitis A, B, or C infection
  • Adequate pulmonary function as defined by forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted by pulmonary function testing
  • Agreement by females of childbearing potential* and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation. The effects of study treatment on a developing fetus have the potential for teratogenic or abortifacient effects. Should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • A female of childbearing potential is defined as a sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months

Who cannot join

  • Prior treatment with leflunomide
  • Prior treatment for smoldering multiple myeloma
  • Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period; current or planned growth factor or transfusion support until after initiation of treatment; if growth factor or transfusion support is provided between screening and start of treatment, the participant will no longer be eligible
  • Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
  • Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL)
  • Renal insufficiency: creatinine clearance < 40 mL per min or serum creatinine > 177 umol/L (> 2 mg/dL)
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  • Anemia: hemoglobin value of > 20 g/L below the lower limit of normal, or a hemoglobin value < 10 g/dL
  • Bone lesions: one or more osteolytic lesions on skeletal radiography, computer tomography (CT), or positron emission tomography (PET)-CT
  • Any one or more of the following biomarkers of malignancy:
  • Clonal bone marrow plasma cell percentage >= 60%
  • Involved: uninvolved serum free light chain ratio >= 100 (Involved free light chain must be >= 100 mg/L) >= 1 focal lesions on magnetic resonance imaging (MRI) studies (>=5 mm in size each)
  • Participants with increased calcium level, renal dysfunction, anemia, and destructive bone lesions (CRAB) criteria that are attributable to conditions other than the disease under study may be eligible
  • Prior diagnosis of rheumatoid arthritis
  • Prior allogeneic transplant
  • Acute active infection requiring systemic therapy within 2 weeks prior to enrollment
  • Pre-existing liver disease
  • Known human immunodeficiency virus (HIV) infection
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to leflunomide and cholestyramine
  • Non-hematologic malignancy within the past 3 years aside from the following exceptions:
  • Adequately treated basal cell or squamous cell skin cancer
  • Carcinoma in situ of the cervix
  • Prostate cancer < Gleason grade 6 with a stable PSA
  • Successfully treated in situ carcinoma of the breast
  • Clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or the patient's ability to give informed consent
  • Pregnant women and women who are lactating; leflunomide has potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is enrolled on this study
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Phase 2 Trial of Leflunomide in Patients With High-Risk Smoldering Multiple Myeloma

This phase II trial studies how well leflunomide works in treating patients with high-risk smoldering multiple myeloma. Leflunomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the anti-myeloma activity of leflunomide, when given as a single agent, as assessed by freedom from progression at 2-years.

SECONDARY OBJECTIVES:

  1. To evaluate the safety and tolerability of single agent leflunomide. II. To summarize and assess toxicities by type, frequency, severity, attribution, time course and duration.

III. To estimate overall and progression-free survival probabilities. IV. To estimate response rate and duration of response. V. To describe the impact of treatment on quality of life, as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score version (v)3.0.

EXPLORATORY OBJECTIVES:

  1. To characterize the molecular evolution of the tumor cells. II. To evaluate whether specific genetic subtypes respond differently to leflunomide.

III. To evaluate the role of immune cells in the progression of smoldering multiple myeloma (SMM).

IV. To evaluate the role of leflunomide in modulating the immune system. V. To examine the relationship between immunological changes and disease progression.

OUTLINE:

Patients receive leflunomide orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 28 days.

Being tested
Leflunomide, Quality-of-Life Assessment, Questionnaire Administration
Medical subject headings
Smoldering Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LeflunomideDrug

    Also called Arava, SU101

    Given PO

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT03952832
Study groupRoleWhat they receive
Treatment (leflunomide)ExperimentalPatients receive leflunomide PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Leflunomide; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression to multiple myeloma

    Progression to multiple myeloma in the absence of increased calcium level, renal dysfunction, anemia, and destructive bone lesions (CRAB) features, orto symptomatic multiple myeloma that requires therapy will be assessed.

    Measured: Up to 2 years

  2. Overall survival

    Overall survival will be estimated using the product-limit method of Kaplan and Meier.

    Measured: Up to 2 years

Secondary outcomes (4)

  1. Overall response rate (ORR)

    The overall response rate and 95% Clopper Pearson binomial confidence interval (CI) will be calculated. Response rates will also be explored based on number/type of prior therapy(ies).

    Measured: Up to 2 years

  2. Incidence of adverse events (AEs)

    Adverse events will be characterized using the descriptions and grading scales found in the most recent version of Common Terminology Criteria for Adverse Events (CTCAE) version (v)5. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

    Measured: Up to 30 days post treatment

  3. Freedom from progression

    Freedom from progression will be estimated using the product-limit method of Kaplan and Meier.

    Measured: Up to 2 years

  4. Change in quality of life

    The quality of life questionnaire (QLQ-C30) scales (five functional scales, three symptom scales, a global health status/ quality of life (QoL) scale, and six single items) will be summarized using descriptive statistics. Changes in reported QOL over time from baseline will also be summarized.

    Measured: Baseline up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2019
  2. Study start11 Dec 2019 (estimated)
  3. Primary completion11 Jun 2021 (estimated)
  4. Study completion11 Jun 2021 (estimated)

Why it stopped: Budget issues

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03952832
Sponsor's protocol ID
18458
Other IDs
NCI-2019-00247, 18458
Status last verified
Nov 2019
First submitted
1 Feb 2019
Last updated
14 Nov 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Leflunomide, Quality-of-Life Assessment and Questionnaire Administration in people with Smoldering Plasma Cell Myeloma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 14 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression to multiple myeloma (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03952832.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2019.

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